RT Journal Article
SR Electronic
T1 A microdosing study with <sup>99m</sup>Tc-PHC-102 for the SPECT/CT imaging of primary and metastatic lesions in renal cell carcinoma patients
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP jnumed.120.245530
DO 10.2967/jnumed.120.245530
A1 Oana Cristina Kulterer
A1 Sarah Pfaff
A1 Wolfgang Wadsak
A1 Nathalie Garstka
A1 Mesut Remzi
A1 Chrysoula Vraka
A1 Lukas Nics
A1 Franziska Bootz
A1 Samuele Cazzamalli
A1 Nikolaus Krall
A1 Dario Neri
A1 Alexander Robert Haug, samuele.ca
YR 2020
UL http://jnm.snmjournals.org/content/early/2020/07/16/jnumed.120.245530.abstract
AB 99mTc-PHC-102 is a 99mTc-labeled derivative of acetazolamide, a high-affinity small organic ligand of Carbonic Anhydrase IX (CAIX). 99mTc-PHC-102 has previously shown favourable in vivo biodistribution properties in mouse models of CAIX-positive clear cell renal cell carcinoma (ccRCC) and colorectal cancer. In this study, we aimed to explore the targeting performance of 99mTc-PHC-102 in single-photon emission computed tomography (SPECT) in patients with RCC, while also assessing the safety and tolerability of the radiotracer. Methods: We studied five patients with localized or metastatic clear cell renal cell carcinoma (ccRCC) in a microdosing regimen, after the administration of 100 µg total CAIX ligand and 600-800 MBq 99mTc-PHC-102. Tissue distribution and residence time in normal organs and tumors were analysed by serial SPECT/CT scans at three time points (30 minutes, 2, and 6 hours) after intravenous administration. Results: In the five patients studied, 99mTc-PHC-102 was well tolerated and no study drug-related adverse events were recorded. The radiotracer showed a rapid initial uptake in the stomach, kidneys and gallbladder, which cleared over time. Localization of the study drug in primary tumors of five patients was observed with favourable tumour-to-background ratios. 99mTc-PHC-102-SPECT/CT allowed the identification of four previously unknown lung and lymph node metastases in two patients. Conclusion: 99mTc-PHC-102 is a promising SPECT tracer for the imaging of patients with clear cell renal cell carcinoma. This tracer has the potential to identify primary and metastatic lesions in different anatomical locations. 99mTc-PHC-102 might also serve as companion diagnostic agent for future CAIX-targeting therapeutics.